The present invention relates to a method and apparatus for monitoring cerebral oxygenation (i.e., a Cerebral Oxygenation Monitor or COM), particularly in the intrauterine environment. The method includes measuring light scattering parameters of light directed through the cerebral cortex.
Fetal brain injury resulting from hypoxia and ischemia during labor is an important cause of death and long-term disability. However, little is known about fetal brain oxygenation and hemodynamics because there are currently no satisfactory clinical techniques for fetal monitoring. There is a need for a new method to assess fetal deep brain oxygenation.
With the United States experiencing unacceptably high infant mortality rates, national health objectives have targeted reductions in infant mortality, fetal death, low birth weight, and severe complications of pregnancy, along with reduction in severe mental retardation, as important goals to be achieved in this decade. However, the attainment of these goals has remained elusive, even with the rising cost of health care.
Obstetrical care continues to be more technology oriented than many other areas of health care. Risk factors are quickly identified, and patients are followed with an array of tools including electronic fetal monitoring (EFM), ultrasound, amniocentesis, and laboratory tests which were virtually unknown 20 years ago. Yet perinatal morbidity and mortality have not yielded to this intensive investment of resources. At least one form of neurologic handicap (cerebral palsy) may be on the rise. An example of perhaps the most obvious unintended and undesirable consequence of the use of surveillance methods has been the drastic increase in the cesarean delivery rate. While the rate is falling, there is still general agreement that the rate is too high and should be lowered if possible. In fact, the national health objectives now include a targeted reduction in the cesarean delivery rate.
As indicated, increasing expenditures for perinatal care have not led to a corresponding reduction in infant mortality, low birth weight deliveries, severe mental retardation, or birth defect rates in the United States. A principal explanation for this lack of progress is the scientific uncertainty surrounding the provision of perinatal care. Significant variation in the practice of medicine, and concomitant variation in health care costs, arise when there is insufficient scientific knowledge to support one alternative over another. Such is the case with the most feared aspect of perinatal morbidity: neurologic handicap, principally cerebral palsy, but also including mental retardation, learning disabilities and epilepsy. For over 100 years, the medical profession has assumed that the circumstances of birth predict which infants will develop cerebral palsy. Until recently, rigorous analyses had failed to confirm this assumption. A recent comprehensive review concluded that it is not possible to predict which babies are at risk for brain disorders and which of the at-risk babies will actually experience problems. Although a 1996 study found that there was an association between abnormal findings on EFM and the risk of cerebral palsy, the false-positive rate was very high.
Regrettably, there is currently no highly sensitive and specific technology to assess fetal well being. Therefore, a method that accurately and reliably categorizes fetal status has the potential to significantly improve perinatal outcomes while managing health care costs.
Intrapartum fetal evaluation is used to prevent neonatal illness and death as well as intrapartum fetal death. Intermittent auscultation was originally utilized for this purpose, and remains acceptable for monitoring xe2x80x9clow riskxe2x80x9d patients. EFM subsequently was touted as a method of evaluation that would lead to decreased cerebral palsy, neonatal and intrapartum death rates. Although it places less of a demand on nursing staff, allows continuous and objective recording of information (fetal and uterine), and allows improved detection of patterns of fetal distress that are missed by auscultation, its benefit over no monitoring has not been proven.
Fetal heart rate patterns of distress may be associated with fetal acidemia, hypoxemia and acidosis. Abnormal fetal heart rate patterns, although a good predictor of fetal distress, are not good predictors of cerebral palsy. EFM is reassuring when normal. When abnormal, correct diagnosis of the problem requires an attendant skilled in EFM interpretation and ancillary procedures such as fetal scalp stimulation and scalp pH monitoring, vibroacoustic stimulation, ultrasound, etc.
The drawback in these methods is that they do not provide a direct assessment of fetal brain oxygenation, which is ultimately the most important variable in determining whether an infant will suffer from long-term neurologic injury or succumb to death. A method of fetal evaluation for those infants with a distress pattern that would allow detection of cerebral hypoxia is needed. The EFM is a screening test. The diagnostic tests detailed above have lead to increasing cesarean section rates with no reduction in cerebral palsy and a minimal reduction in intrapartum death.
A testing modality that would allow clinicians a more direct method of evaluating cerebral oxygenation would target the hypoxic fetus and thus reduce the number of unnecessary cesarean sections performed for the misperception of xe2x80x9cfetal distress,xe2x80x9d and in turn decrease maternal morbidity and mortality, as well as length of hospital stay and, thus, lower medical costs.
An instrument according to different aspects of the present invention addresses at least three different clinical needs. The first is continuous non-invasive monitoring of fetal cerebral oxygenation during labor and delivery. This requires a small, unobtrusive, bedside instrument.
A second aspect of the invention is a postpartum imager. The imager has a position sensor on the probe and a high resolution video display. Images will resemble diagnostic ultrasound B-scans. The technology used in the postpartum imager utilizes identical laser light sources, detectors and signal processing as the COM. A three dimensional image is produced by overlaying many individual COM readings taken from different volumes of the newborn head on a display. The different sample volumes can be obtained in two ways. First, a source-detector pair can be positioned at different locations on the head similar to an ultrasound B-scan. Alternatively, an array of source-detector pairs can take a sequence of sample volumes similar to computed tomography.
The third aspect of the invention is an antepartum monitor. Because the instrument can penetrate 8-10 cm of tissue, fetal cerebral oxygenation images can be obtained through the mothers abdomen. The principle of the antepartum imager is identical to the postpartum imager. The specially conditioned laser light penetrates the additional soft tissue of the mother and the same banana shaped sample volume is measured. Roughly 50% of the middle of the sample volume is fetal cerebral tissue. Fetal tissue is differentiated from maternal tissue on the resulting three dimensional image by the dark outline of the fetal skull.
Comparison of the Present Invention with Fetal Pulse Oximeters
Fetal pulse oximeters have been in development for several years. This device utilizes a modification of adult finger probe transmission technology to perform reflectance pulse oximetry on intrauterine fetal cheeks. The probe is attached to the fetal cheek and held in place by pressure from the uterine wall. However, investigators outside of the United States have been evaluating fetal pulse oximeters for several years and conclude that the current generation of fetal pulse oximetry sensors is not improving the quality of combined monitoring of fetal heart rate and fetal scalp blood analysis. This is not the case for a COM according to the present invention as shown in the following comparison with the fetal pulse oximeter.
COM is a near infrared spectrometer (NIRS) that uses laser diodes for the optical source. Laser diodes have adequate power at a specific wavelength to penetrate fetal hair, scalp, and skull into deep gray and white matter, while remaining comfortably within the safety standards. Fetal pulse oximeters use LEDs for optical sources that emit a weaker broad spectrum light beam. The significance of the difference in optical source lies in the ability of COM to measure the lower cerebral tissue oxygenation rather than the cheek saturation measured with fetal oximeters. A second difference is that the COM intrauterine probe is held in place by suction, which has been shown to effectively maintain contact.
Spectrometers
The analysis of absorption and scattering properties of deep brain tissue is an important problem in fetal and neonatal health, in particular for determining chromophore concentrations in tissue of hemoglobin (Hb), oxyhemoglobin (HbO2) and cytochrome oxidase. Conventional near infrared spectrometers (NIRS) allow the changes in chromophore concentrations to be calculated from changes in the light intensity diffusely reflected from the tissue surface. However, the absolute concentrations of these chromophores, i.e. the absolute absorption coefficient, cannot easily be inferred as the scattering of the light in the tissue must be taken into account.
The following documents include information generally related to the present invention, and are all incorporated in their entirety by reference:
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11. A. M. Vintzileos MD, A. Antsaklis MD, I. Varvarigos MD, C. Papas MD, I. Sofatzis MD, J. T. Montgomery RN xe2x80x9cA randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation,xe2x80x9d Obstet Gynecol 81(6), 899-907 (1993).
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None of the above documents are admitted to anticipate or render obvious in any combination the present invention, but are included to help place the present invention in context.
A method and apparatus for determining the total hemoglobin and saturation, and absolute Hb and HbO2 concentrations are provided. Total hemoglobin is the sum of all the different types of hemoglobin. Hb concentration is the amount of deoxygenated blood and HbO2 concentration indicates how much oxygenated blood is present. The significance of absolute HbO2 concentrations is it quantifies the amount of oxygen in the tissue. Significant concentrations of Hb indicates the tissue is not being oxygenated properly. Absolute hemoglobin concentrations quantify the amount of hemoglobin and oxygen is tissue.
The measurement of these parameters provides significantly more information than Saturation, the ratio of HbO2 to total hemoglobin. The Saturation ratio does not indicate how much hemoglobin or oxygen is present. An instrument according to the present invention is significantly less complex than conventional near infrared spectrometers, because it measures slight changes in tissue absorption produced by small optical source wavelength changes. In a preferred application, the instrument gives an early-warning of cerebral injury through intrauterine monitoring. The instrument will also lower the cost of health care delivery because it is estimated that 25%-35% of all C-sections could be avoided with the monitoring capability provided by the invention.
In a preferred application, a probe is placed over a fetal scalp for probing through the skull into the cortex. Probe components include the probe body containing a light source, common detector, and a cable leading from the probe body to the monitor. The probe body consists of a flexible circuit with electrical contacts for the detector and cable. The flexible circuit is preferably encapsulated in an optical grade silicon which allows the probe to conform to the curvature of the skull. Light passes through the cortex in a banana shaped path from the light source to the common detector. Reflected light is measured at the detector, amplified and transmitted via the cable to the monitor. It should be apparent that one or more sources and one or more detectors could be used in any combination, and that in the invention as claimed a reference to xe2x80x9ca detectorxe2x80x9d will be construed to include more than one detector and a reference to multiple detectors will be construed to include one detector operating a multiple wavelengths.
The cerebral oxygenation monitor (COM) according to the present invention allows evaluation of deep gray and white matter of the fetal brain, and measures brain tissue saturation, Hb and HbO2. This is an improvement over the new fetal pulse oximeters (which measure arterial saturation) at an equivalent cost. The COM is a diagnostic test that is in one embodiment noninvasive to the fetus (rupture membranes required for its placement) to be used in those patients where EFM suggests the fetus is at risk. The parameters measured may provide vital information including: evaluation of xe2x80x9cfetal distressxe2x80x9d patternsxe2x80x94knowing brain tissue oxygen saturation will more precisely determine whether the fetus is at true risk of long-term neurologic injury or death; and evaluation of total hemoglobinxe2x80x94in infants anemic due to iso-immunization or vasa previa, possible conservative management of their delivery could be allowed. The COM thus is of great potential value in obstetrics. Intermittent and continuous use of its parameters in the xe2x80x9cat riskxe2x80x9d fetus may facilitate an improvement in fetal and maternal health.
Optimal Spectroscopic Source: Vertical Cavity Surface Emitting Lasers
The COM may utilize vertical cavity surface emitting laser (VCSEL) optical sources that have many important advantages over other types of lasers. A VCSEL approach may be selected for COM because: VCSELs are inherently much simpler than other optical source systems; the emission wavelength of VCSELs is controlled by temperature rather than a mechanical system; VCSELs are small and low cost because they are manufactured with bulk semiconductor technology; VCSELs can be attached directly to the fetal head rather than through a fiber; VCSELs are low power but can be built in arrays that meet the power requirements to penetrate fetal hair and bone; and VCSELs at different wavelengths can be placed on the same probe. In this manner, an aspect of the invention includes simultaneously measuring at two wavelengths, such as 760 nm and 830 nm, wherein both arrays are mounted in a single fetal probe. The use of VCSELs is a system similar to the disclosed system is believed to be unknown in the prior art, and represents an important technical advance.
Technical Rationale
Different experimental approaches have been developed for the measurement of absolute absorption coefficients (xcexca) and scattering coefficients (xcexcsxe2x80x2), in highly scattering media. Reflected intensity measurements for different distances between light source and detector can be used. Alternatively, measurements can be based upon the time of flight of the light in tissue in addition to the reflectance. Intensity modulated laser spectrometers (IMLS) are an alternative to time resolved systems, and provide measurements of the phase and the modulation depth of an intensity modulated light wave. The phase difference is approximately proportional to the mean time of flight of the light in the medium. It has been shown that, for a fixed modulation frequency, xcexca and xcexcsxe2x80x2 can be inferred from the intensity and phase data obtained at different source detector distances. Alternatively, single distance, multiple modulation frequency measurements can be used. All of these methods are based upon fitting xcexca and xcexcsxe2x80x2 to diffusion equation solutions for light transport in the medium.
The present invention includes a method for the determination of absorption coefficients. The basic premise is that small changes in the absorption coefficient induce changes in diffuse light intensity, phase, and modulation depth, and that the ratio of these changes is primarily independent of the scattering properties of the medium. This ratio provides a good estimate of the absolute absorption coefficient. The approximation is only valid over a certain range of xcexca and xcexcsxe2x80x2 values, however it encompasses the range found in biological tissues for near infrared wavelengths. Similarly, the ratio of the changes in intensity and phase, induced by variation in the source wavelength, allows xcexca to be estimated. Furthermore, xcexcsxe2x80x2 can be inferred based upon the estimated xcexca value. The main advantages of the suggested method for the in vivo monitoring of hemoglobin concentration and oxygen saturation is its simplicity. Source-detector distance remains constant, there is no expensive time-of-flight instrumentation and no multiple modulation schemes.